Monday, December 24, 2007

fasting.pdf fasting "high" caused by ketones, similar to GHB, which treats narcolepsy, alcoholism and opiod addiction

Summary Anecdotal evidence links the initial phase of fasting or a low-carbohydrate diet with feelings of well-beingand mild euphoria. These feelings have often been attributed to ketosis, the production of ketone bodies which canreplace glucose as an energy source for the brain. One of these ketone bodies, b-hydroxybutyrate (BHB), is an isomer ofthe notorious drug of abuse, GHB (c-hydroxybutyrate). GHB is also of interest in relation to its potential as a treatmentfor alcohol and opiate dependence and narcolepsy-associated cataplexy. Here I hypothesize that, the mild euphoriaoften noted with fasting or low-carbohydrate diets may be due to shared actions of BHB and GHB on the brain.Specifically, I propose that BHB, like GHB, induces mild euphoria by being a weak partial agonist for GABABreceptors.I outline several approaches that would test the hypothesis, including receptor binding studies in cultured cells,perception studies in trained rodents, and psychometric testing and functional magnetic resonance imaging in humans.These and other studies investigating whether BHB and GHB share common effects on brain chemistry and mood aretimely and warranted, especially when considering their structural similarities and the popularity of ketogenic dietsand GHB as a drug of abuse.

Since recorded time, across many cultures, fastinghas been used in rituals aimed at attaining a higherstate of being. Fasting for religious and spiritualreasons has been mentioned in the Bible, bothOld and New Testaments, the Koran and the Mahabharata[1]. Anecdotal feelings of well-being andmild euphoria also litter the popular literature onlow-carbohydrate diets. For example, one diaristwrote after 2–3 days on the Atkin’s Diet: ‘‘It isnot an unpleasant feeling, a sort of mild, foggyeuphoria’’. [2]. From an evolutionary perspective,mild euphoria associated with short-term fastingmay ease anxiety and aid the search for food. Ketosisoccurs during the first few days of fasting or alow-carbohydrate diet, when breakdown of fat (boxidation)outstrips breakdown of carbohydrate(glycolysis). Three ketone bodies are produced bythe liver:

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After 2–3 days of fasting BHB reachesmillimolar levels in the blood and brain [3], and togetherwith acetoacetate provides the brain withan alternative energy source to glucose. Severalbiochemical explanations have been proposed forthe feelings of euphoria often associated withshort-term total fasting or low-carbohydrate diets.Bloom [4] postulated that accumulation of acetoacetateproduces a mild intoxication similar to ethanol.Phillips [5] speculated from his studies indairy cows that the accumulation of isopropyl alcohol(a byproduct of acetone metabolism) in neuraltissue might be responsible for fasting-induced religious,mystical or hallucinatory experiences.HypothesisHere I propose that diet-induced euphoria may involveproduction of BHB, and may be at least partiallyexplained by the well-known psychologicaleffects of its isomer, c-hydroxybutyrate (GHB)(Fig. 1). Considering their structural similarities,it is perhaps surprising that no one has linked BHBand GHB before.